Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and man. They provide a plausible set of equations that can be used to extrapolate data from animals to man and thereby improve chemotherapy, and risk assessment. Increased emphasis has been placed on regional drug administration, in particular intrathecal, intraperitoneal and intra-arterial. The former two modes have required the development of spatially distributed models of the tissue adjacent to the cerebrospinal fluid (CSF) or peritoneal fluid. These analyses have provided considerable insight into the penetration depths of drugs administered by these routes and the interpretation of CSF kinetics in terms of brain concentration profiles. The penetration of cis-dichlorodiammine-platinum (II) (DDP) into peritoneal and subperitoneal tissue is being examined experimentally with an electron probe and the results compared with a reaction-diffusion equation of the process. A lumped model of DDP pharmacokinetics is also being developed to include both metabolism to a mobile species and covalent binding to macromolecules. Pharmacokinetic theory has been developed for intra-arterial drug administration combined with hemoperfusion of vascular drainage, and the concepts have been validated experimentally in monkeys. A clinical trial is in progress.